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The Genetic Architecture of Vitamin D Deficiency among an Elderly Lebanese Middle Eastern Population: An Exome-Wide Association Study

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submitted on 2024-08-20, 04:54 and posted on 2024-08-20, 04:56 authored by Nagham Nafiz Hendi, Marlene Chakhtoura, Yasser Al-Sarraj, Dania Saleh Basha, Omar Albagha, Ghada El-Hajj Fuleihan, Georges Nemer

The Middle East region experiences a high prevalence of vitamin D deficiency, yet most genetic studies on vitamin D have focused on European populations. Furthermore, there is a lack of research on the genomic risk factors affecting elderly people, who are more susceptible to health burdens. We investigated the genetic determinants of 25-hydroxyvitamin D concentrations in elderly Lebanese individuals (n = 199) through a whole-exome-based genome-wide association study. Novel genomic loci displaying suggestive evidence of association with 25-hydroxyvitamin D levels were identified in our study, including rs141064014 in the MGAM (p-value of 4.40 × 10−6) and rs7036592 in PHF2 (p-value of 8.43 × 10−6). A meta-analysis of the Lebanese data and the largest European genome-wide association study confirmed consistency replication of numerous variants, including rs2725405 in SLC38A10 (p-value of 3.73 × 10−8). Although the polygenic risk score model derived from European populations exhibited lower performance than European estimations, it still effectively predicted vitamin D deficiency among our cohort. Our discoveries offer novel perspectives on the genetic mechanisms underlying vitamin D deficiency among elderly Middle Eastern populations, facilitating the development of personalized approaches for more effective management of vitamin D deficiency. Additionally, we demonstrated that whole-exome-based genome-wide association study is an effective method for identifying genetic components associated with phenotypes.

Other Information

Published in: Nutrients
License: https://creativecommons.org/licenses/by/4.0/
See article on publisher's website: https://dx.doi.org/10.3390/nu15143216

History

Language

  • English

Publisher

MDPI

Publication Year

  • 2023

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • College of Health and Life Sciences - HBKU
  • Qatar Genome Program (2015-2024)

Geographic coverage

Lebanon